Dopaminergic modulation of axon initial segment calcium channels regulates action potential initiation.

Abstract:

:Action potentials initiate in the axon initial segment (AIS), a specialized compartment enriched with Na(+) and K(+) channels. Recently, we found that T- and R-type Ca(2+) channels are concentrated in the AIS, where they contribute to local subthreshold membrane depolarization and thereby influence action potential initiation. While periods of high-frequency activity can alter availability of AIS voltage-gated channels, mechanisms for long-term modulation of AIS channel function remain unknown. Here, we examined the regulatory pathways that control AIS Ca(2+) channel activity in brainstem interneurons. T-type Ca(2+) channels were downregulated by dopamine receptor activation acting via protein kinase C, which in turn reduced neuronal output. These effects occurred without altering AIS Na(+) or somatodendritic T-type channel activity and could be mediated by endogenous dopamine sources present in the auditory brainstem. This pathway represents a new mechanism to inhibit neurons by specifically regulating Ca(2+) channels directly involved in action potential initiation.

journal_name

Neuron

journal_title

Neuron

authors

Bender KJ,Ford CP,Trussell LO

doi

10.1016/j.neuron.2010.09.026

subject

Has Abstract

pub_date

2010-11-04 00:00:00

pages

500-11

issue

3

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(10)00768-3

journal_volume

68

pub_type

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